ArticleArchives of medical science : AMS2015
Impact of peroxisome proliferator-activated receptor γ on angiotensin II type 1 receptor-mediated insulin sensitivity, vascular inflammation and atherogenesis in hypercholesterolemic mice.
Article in Archives of medical science : AMS, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed, 5 citations in OpenAlex.
- Effects of Statins on Renin-Angiotensin System.Journal of cardiovascular development and disease · 2021Review
- C-reactive protein levels predict systolic heart failure and outcome in patients with first ST-elevation myocardial infarction treated with coronary angioplasty.Archives of medical science : AMS · 2017Article
- Genetic disruption of multidrug resistance-associated protein 1 improves endothelial function and attenuates atherosclerosis in MRP1Archives of medical science : AMS · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe angiotensin II type 1 receptor (AT1R) and the peroxisome proliferator-activated receptor γ (PPARγ) have been implicated in the pathogenesis of atherosclerosis. A number of studies have reported that AT1R inhibition or genetic AT1R disruption and PPARγ activation inhibit vascular inflammation and improve glucose and lipid metabolism, underscoring a molecular interaction of AT1R and PPARγ. We here analyzed the hypothesis that vasculoprotective anti-inflammatory and metabolic effects of AT1R inhibition are mediated by PPARγ. MATERIAL AND
methodsFemale ApoE(-/-)/AT1R(-/-) mice were fedwith a high-fat and cholesterol-rich diet and received continuous treatment with the selective PPARγ antagonist GW9662 or vehicle at a rate of 700 ng/kg/min for 4 weeks using subcutaneously implanted osmotic mini-pumps. Additionally, one group of female ApoE(-/-) mice served as a control group. After treatment for 4 weeks mice were sacrificed and read-outs (plaque development, vascular inflammation and insulinsensitivity) were performed.
resultsUsing AT1R deficient ApoE(-/-) mice (ApoE(-/-)/AT1R(-/-) mice) we found decreased cholesterol-induced endothelial dysfunction and atherogenesis compared to ApoE(-/-) mice. Inhibition of PPARγ by application of the specific PPARγ antagonist GW9662 significantly abolished the anti-atherogenic effects of AT1R deficiency in ApoE(-/-)/AT1R(-/-) mice (plaque area as % of control: ApoE(-/-): 39 ±5%; ApoE(-/-)/AT1R(-/-): 17 ±7%, p = 0.044 vs. ApoE(-/-); ApoE(-/-)/AT1R(-/-) + GW9662: 31 ±8%, p = 0.047 vs. ApoE(-/-)/AT1R(-/-)). Focusing on IL6 as a pro-inflammatory humoral marker we detected significantly increased IL-6 levels in GW9662-treated animals (IL-6 in pg/ml: ApoE(-/-): 230 ±16; ApoE(-/-)/AT1R(-/-): 117 ±20, p = 0.01 vs. ApoE(-/-); ApoE(-/-)/AT1R(-/-) + GW9662: 199 ±20, p = 0.01 vs. ApoE(-/-)/AT1R(-/-)), while the anti-inflammatory marker IL-10 was significantly reduced after PPARγ inhibition in GW9662 animals (IL-10 in pg/ml: ApoE(-/-): 18 ±4; ApoE(-/-)/AT1R(-/-): 55 ±12, p = 0.03 vs. ApoE(-/-); ApoE(-/-)/AT1R(-/-) + GW9662: 19 ±4, p = 0.03 vs. ApoE(-/-)/AT1R(-/-)). Metabolic parameters of glucose homeostasis (glucose and insulin tolerance test) were significantly deteriorated in ApoE(-/-)/AT1R(-/-) mice treated with GW9662 as compared to vehicle-treated ApoE(-/-)/AT1R(-/-) mice. Systolic blood pressure and plasma cholesterol levels were similar in all groups.
conclusionsGenetic disruption of the AT1R attenuates atherosclerosis and improves endothelial function in an ApoE(-/-) mouse model of hypercholesterolemia-induced atherosclerosis via PPARγ, indicating a significant role of PPARγ in reduced vascular inflammation, improvement of insulin sensitivity and atheroprotection of AT1R deficiency.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.